The objective of this career development award is to provide the candidate with a mentored environment in which to develop expertise in the epidemiology of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Through graduate coursework and other structured activities, the candidate will: 1) strengthen her knowledge of endocrinology, focusing on the metabolism and physiology of vitamin D, calcium, and parathyroid hormone and their relationship to PMS and PMDD;2) develop an understanding of how hormones affect neurologic function and are involved in the etiology of affective disorders such as PMDD;3) develop expertise in mental health and psychiatric epidemiology relating to affective disorders such as PMDD;and 4) expand her skills as an epidemiologist to include the use of genetic factors and biochemical markers in epidemiology. In addition, the candidate will complete a research project to assess the relationship between plasma and genetic factors and the incidence of PMS/PMDD. This project will build upon the interesting findings of a preliminary study which suggested that women who had high intakes of vitamin D and calcium had significant 30-40 percent reductions in risk of developing PMS. Specific aims of the research plan are to: 1) evaluate the relationship between luteal phase plasma levels of 25-hydroxyvitamin D, 1, 25-dihydroxyvitamin D, calcium and PTH and risk of PMS/PMDD;2) evaluate whether common vitamin D receptor polymorphisms including Fok1, Bsm1, Apa1, and Taq1 affect risk of PMS/PMDD;and 3) evaluate whether age and genotype may modify the relationship between plasma vitamin D, calcium and PTH levels and incidence of PMS/PMDD. This will be the first prospective and most comprehensive study of these relationships conducted to date. Overall, this career development award will provide the candidate with the skills she needs to achieve her goals of becoming an independent epidemiologist who can contribute significantly to knowledge of PMS/PMDD etiology, assessment, prevention and treatment. Relevance to public health: This will be the first prospective study of the role of vitamin D, calcium and PTH in PMS and PMDD, disorders that cause substantial levels of impairment in large numbers of premenopausal women. The identification of modifiable factors that reduce PMS/PMDD incidence will provide women opportunities for reducing their risk with fewer drawbacks than current treatment options.